dbSNP rs144632372: BCAT1:p.Glu348Gln (chr12-24832725-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_005504.7(BCAT1):c.1042G>C(p.Glu348Gln) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000689 in 1,450,888 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E348K) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

BCAT1
NM_005504.7 missense, splice_region

Scores

Splicing: ADA: 0.00007186

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.385

Variant links:

Genes affected

BCAT1 (HGNC:976): (branched chain amino acid transaminase 1) This gene encodes the cytosolic form of the enzyme branched-chain amino acid transaminase. This enzyme catalyzes the reversible transamination of branched-chain alpha-keto acids to branched-chain L-amino acids essential for cell growth. Two different clinical disorders have been attributed to a defect of branched-chain amino acid transamination: hypervalinemia and hyperleucine-isoleucinemia. As there is also a gene encoding a mitochondrial form of this enzyme, mutations in either gene may contribute to these disorders. Alternatively spliced transcript variants have been described. [provided by RefSeq, May 2010]

BCAT1 links:

ENSG00000256482 (HGNC:58192):

ENSG00000256482 links:

LOC105369699 (HGNC:):

LOC105369699 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0419209).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCAT1	NM_005504.7 link	c.1042G>C	p.Glu348Gln	missense_variant, splice_region_variant	Exon 9 of 11	ENST00000261192.12	NP_005495.2	P54687-1A0A024RAV0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCAT1	ENST00000261192.12 link	c.1042G>C	p.Glu348Gln	missense_variant, splice_region_variant	Exon 9 of 11	1	NM_005504.7	ENSP00000261192.7		P54687-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.89e-7

AC:

AN:

1450888

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

720998

show subpopulations

Gnomad4 AFR exome

AF:

0.0000302

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.77

CADD

Benign

DANN

Benign

0.61

DEOGEN2

Benign

0.23

T;.;.;.;.

Eigen

Benign

-0.94

Eigen_PC

Benign

-0.93

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.81

T;T;D;T;D

M_CAP

Benign

0.0058

MetaRNN

Benign

0.042

T;T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.74

N;.;.;.;.

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.23

N;N;N;N;N

REVEL

Benign

0.065

Sift

Benign

0.63

T;T;T;T;T

Sift4G

Benign

0.52

T;T;T;T;T

Polyphen

0.013

B;.;.;.;.

Vest4

0.055

MutPred

0.38

Gain of methylation at K346 (P = 0.1019);.;.;.;.;

MVP

0.22

MPC

0.023

ClinPred

0.20

GERP RS

0.40

Varity_R

0.23

gMVP

0.69

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000072

dbscSNV1_RF

Benign

0.024

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over